PDB-8v0b: Structure of TDP1 catalytic domain complexed with compound IB05

ID or keywords:

Entry

Database: PDB / ID: 8v0b

Title

Structure of TDP1 catalytic domain complexed with compound IB05

Components

Tyrosyl-DNA phosphodiesterase 1

Keywords

DNA BINDING PROTEIN / HYDROLASE/INHIBITOR / phosphodiesterase / drug target / cancer / HYDROLASE-INHIBITOR complex

Function / homology

Function and homology information

3'-tyrosyl-DNA phosphodiesterase activity / Hydrolases; Acting on ester bonds; Phosphoric-diester hydrolases / single strand break repair / exonuclease activity / Nonhomologous End-Joining (NHEJ) / double-strand break repair / single-stranded DNA binding / double-stranded DNA binding / DNA repair / intracellular membrane-bounded organelle ...
Similarity search - Function

Biological species

Homo sapiens (human)

Method

X-RAY DIFFRACTION /

SYNCHROTRON /

MOLECULAR REPLACEMENT / Resolution: 1.65 Å

Authors

Lountos, G.T. / Zhao, X.Z. / Barakat, I. / Wang, W. / Agama, K. / Al Mahmud, M.R. / Pommier, Y. / Burke Jr., T.R.

Funding support

United States, 1items

Citation

Journal: To Be Published
Title: Structures of TDP1 complexed with inhibitors
Authors: Lountos, G.T. / Zhao, X.Z. / Barakat, I. / Wang, W. / Agama, K. / Al Mahmud, M.R. / Pommier, Y. / Burke Jr., T.R.

History

Deposition	Nov 17, 2023	Deposition site: RCSB / Processing site: RCSB
Revision 1.0	Sep 25, 2024	Provider: repository / Type: Initial release

Structure viewer	Molecule: MolmilJmol/JSmol

-
Download

PDBx/mmCIF format	8v0b.cif.gz	391.1 KB	Display	PDBx/mmCIF format
PDB format	pdb8v0b.ent.gz	318 KB	Display	PDB format
PDBx/mmJSON format	8v0b.json.gz		Tree view	PDBx/mmJSON format
Others	Other downloads

-
Validation report

Summary document	8v0b_validation.pdf.gz	987 KB	Display	wwPDB validaton report
Full document	8v0b_full_validation.pdf.gz	999.4 KB	Display
Data in XML	8v0b_validation.xml.gz	47.2 KB	Display
Data in CIF	8v0b_validation.cif.gz	65.7 KB	Display
Arichive directory	https://data.pdbj.org/pub/pdb/validation_reports/v0/8v0b ftp://data.pdbj.org/pub/pdb/validation_reports/v0/8v0b	HTTPS FTP

-
Related structure data

Related structure data	8v0cC C: citing same article (ref.)
Similar structure data	Similarity search - Function & homologyF&H Search Similarity search - FunctionF&H Search Similarity search - HomologyF&H Search

-
Links

PDB pages	PDBj / wwPDB / NCBI
Related items in Molecule of the Month	#234 - Jun 2019 MDM2 and Cancer similarity (1) #55 - Jul 2004 DNA Ligase similarity (1) #241 - Jan 2020 Twenty Years of Molecules similarity (1)

Deposited unit

A: Tyrosyl-DNA phosphodiesterase 1

B: Tyrosyl-DNA phosphodiesterase 1

hetero molecules

106 kDa, 2 polymers
Search similar-shape structures of this assembly by Omokage search (details)

1

A: Tyrosyl-DNA phosphodiesterase 1

hetero molecules

defined by author
53 kDa, 1 polymers
Search similar-shape structures of this assembly by Omokage search (details)

2

B: Tyrosyl-DNA phosphodiesterase 1

hetero molecules

defined by author
52.8 kDa, 1 polymers
Search similar-shape structures of this assembly by Omokage search (details)

Unit cell

Length a, b, c (Å)	49.937, 104.531, 192.839
Angle α, β, γ (deg.)	90.00, 90.00, 90.00
Int Tables number	19
Space group name H-M	P2₁2₁2₁

-
Protein , 1 types, 2 molecules AB

#1: Protein	Tyrosyl-DNA phosphodiesterase 1 / Tyr-DNA phosphodiesterase 1 Mass: 52126.336 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: TDP1 / Plasmid: pDN2454 / Production host: Escherichia coli (E. coli) References: UniProt: Q9NUW8, Hydrolases; Acting on ester bonds; Phosphoric-diester hydrolases

#1: Protein

Tyrosyl-DNA phosphodiesterase 1 / Tyr-DNA phosphodiesterase 1

Mass: 52126.336 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.)

Homo sapiens (human) / Gene: TDP1 / Plasmid: pDN2454 / Production host:

Escherichia coli (E. coli)
References: UniProt: Q9NUW8, Hydrolases; Acting on ester bonds; Phosphoric-diester hydrolases

-
Non-polymers , 5 types, 690 molecules

#2: Chemical	ChemComp-YCI / 8-{4-[(fluorosulfonyl)oxy]phenyl}-4-oxo-1,4-dihydroquinoline-3-carboxylic acid Mass: 363.317 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C₁₆H₁₀FNO₆S / Feature type: SUBJECT OF INVESTIGATION
#3: Chemical	ChemComp-EDO / 1,2-ETHANEDIOL / ETHYLENE GLYCOL Mass: 62.068 Da / Num. of mol.: 8 / Source method: obtained synthetically / Formula: C₂H₆O₂
#4: Chemical	ChemComp-DMS / DIMETHYL SULFOXIDE Mass: 78.133 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C₂H₆OS / Comment: DMSO, precipitant*YM
#5: Chemical	ChemComp-PEG / DI(HYDROXYETHYL)ETHER Mass: 106.120 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C₄H₁₀O₃
#6: Water	ChemComp-HOH / water Mass: 18.015 Da / Num. of mol.: 676 / Source method: isolated from a natural source / Formula: H₂O

-
Details

Has ligand of interest	Y

-
Experiment

Experiment	Method: X-RAY DIFFRACTION / Number of used crystals: 1

-
Sample preparation

Crystal	Density Matthews: 2.41 Å³/Da / Density % sol: 49.04 %
Crystal grow	Temperature: 293 K / Method: vapor diffusion, hanging drop Details: 0.1 M MOPS/HEPES-Na pH 7.5, 10% (w/v) PEG 8000, 20% (v/v) ethylene glycol, 0.03 M sodium fluoride, 0.03 M sodium bromide, 0.03 M sodium iodide

-
Data collection

Diffraction	Mean temperature: 100 K / Serial crystal experiment: N
Diffraction source	Source: SYNCHROTRON / Site: APS / Beamline: 22-BM / Wavelength: 1 Å
Detector	Type: MARMOSAIC 300 mm CCD / Detector: CCD / Date: Dec 16, 2021
Radiation	Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelength	Wavelength: 1 Å / Relative weight: 1
Reflection	Resolution: 1.65→50 Å / Num. obs: 121541 / % possible obs: 99.6 % / Redundancy: 6.9 % / CC_1/2: 0.997 / CC star: 0.999 / R_pim(I) all: 0.031 / R_sym value: 0.076 / Net I/σ(I): 25
Reflection shell	Resolution: 1.65→1.68 Å / Redundancy: 5.8 % / Mean I/σ(I) obs: 2 / Num. unique obs: 5861 / CC_1/2: 0.872 / CC star: 0.965 / R_pim(I) all: 0.269 / R_sym value: 0.611 / % possible all: 96.9

-
Processing

Software

Name	Version	Classification
PHENIX	1.16_3549	refinement
HKL-3000		data reduction
HKL-3000		data scaling
PHASER		phasing

Refinement

Method to determine structure:

MOLECULAR REPLACEMENT / Resolution: 1.65→40.552 Å / SU ML: 0.14 / Cross valid method: FREE R-VALUE / σ(F): 1.37 / Phase error: 18.82 / Stereochemistry target values: ML

	R_factor	Num. reflection	% reflection
R_free	0.1883	2000	1.65 %
R_work	0.1641	-	-
obs	0.1645	121441	99.56 %

Solvent computation

Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL

Refinement step

Cycle: LAST / Resolution: 1.65→40.552 Å

	Protein	Nucleic acid	Ligand	Solvent	Total
Num. atoms	7055	0	104	676	7835

Refine LS restraints

Refine-ID	Type	Dev ideal	Number
X-RAY DIFFRACTION	f_bond_d	0.006	7695
X-RAY DIFFRACTION	f_angle_d	0.832	10493
X-RAY DIFFRACTION	f_dihedral_angle_d	6.097	6132
X-RAY DIFFRACTION	f_chiral_restr	0.055	1080
X-RAY DIFFRACTION	f_plane_restr	0.006	1340

LS refinement shell

Resolution (Å)	R_factor R_free	Num. reflection R_free	R_factor R_work	Num. reflection R_work	Refine-ID	% reflection obs (%)
1.65-1.6929	0.2603	136	0.2362	8133	X-RAY DIFFRACTION	96
1.6929-1.7387	0.224	141	0.2096	8422	X-RAY DIFFRACTION	99
1.7387-1.7899	0.2048	142	0.1877	8472	X-RAY DIFFRACTION	100
1.7899-1.8476	0.1902	142	0.1708	8475	X-RAY DIFFRACTION	100
1.8476-1.9137	0.1763	142	0.1683	8457	X-RAY DIFFRACTION	100
1.9137-1.9903	0.2519	142	0.1686	8484	X-RAY DIFFRACTION	100
1.9903-2.0809	0.2141	142	0.1558	8498	X-RAY DIFFRACTION	100
2.0809-2.1906	0.1949	143	0.1574	8519	X-RAY DIFFRACTION	100
2.1906-2.3278	0.1659	141	0.1575	8480	X-RAY DIFFRACTION	100
2.3278-2.5075	0.1885	144	0.1633	8564	X-RAY DIFFRACTION	100
2.5075-2.7598	0.2007	144	0.1681	8586	X-RAY DIFFRACTION	100
2.7598-3.159	0.1943	144	0.1682	8608	X-RAY DIFFRACTION	100
3.159-3.9795	0.1767	146	0.1532	8692	X-RAY DIFFRACTION	100
3.9795-40.5	0.1655	151	0.1557	9051	X-RAY DIFFRACTION	100

Refinement TLS params.

Method: refined / Refine-ID: X-RAY DIFFRACTION

ID	L11 (°²)	L12 (°²)	L13 (°²)	L22 (°²)	L23 (°²)	L33 (°²)	S11 (Å °)	S12 (Å °)	S13 (Å °)	S21 (Å °)	S22 (Å °)	S23 (Å °)	S31 (Å °)	S32 (Å °)	S33 (Å °)	T11 (Å²)	T12 (Å²)	T13 (Å²)	T22 (Å²)	T23 (Å²)	T33 (Å²)	Origin x (Å)	Origin y (Å)	Origin z (Å)
1	1.5323	-0.2467	0.2063	1.1235	-0.4161	1.6248	-0.0753	-0.208	0.0967	0.0902	0.0397	0.0853	-0.0942	-0.1989	0.0368	0.1151	0.0257	-0.003	0.1299	-0.0072	0.1207	1.688	-0.1974	-35.5837
2	1.4151	0.024	0.3408	1.0646	0.0301	2.21	-0.1236	0.0323	0.2304	-0.0604	0.0203	0.1114	-0.286	-0.2837	0.0663	0.0851	0.0155	-0.0195	0.0888	0.0063	0.1516	5.2393	3.3743	-47.3882
3	1.9586	-0.4245	-0.0564	1.2242	-0.197	1.9485	0.0435	0.13	-0.1306	-0.1009	-0.0369	0.1221	0.1479	-0.1797	0.0117	0.0969	-0.0311	-0.0282	0.1029	0.0056	0.1141	1.4244	-8.4162	-53.8331
4	2.9432	0.5365	0.2273	3.5165	-0.4569	1.9144	-0.0171	0.3531	-0.3677	-0.3268	-0.0312	-0.1054	0.548	0.2834	0.0962	0.2103	0.0542	0.0052	0.1845	-0.0337	0.2017	21.0148	-20.1327	-51.5192
5	1.0202	-0.0092	0.403	0.1971	-0.0304	1.2212	0.0429	-0.0438	-0.1381	0.0228	-0.0228	-0.008	0.2746	0.0856	-0.012	0.1443	0.0079	-0.0028	0.0907	0.0217	0.1447	17.9802	-15.1701	-40.1151
6	1.7317	-0.0519	-0.0005	0.4792	-0.2658	4.9084	0.0317	-0.039	0.0395	0.1267	-0.0818	-0.0233	-0.1055	0.3131	0.0593	0.0928	0.0039	-0.0035	0.1398	0.0095	0.1688	24.4286	-9.1588	-35.1487
7	1.6355	-0.0024	0.6836	1.0382	-0.5271	2.5619	-0.016	0.3332	0.1885	-0.0945	-0.1973	-0.2031	-0.2147	0.5216	0.0882	0.157	-0.0454	0.0049	0.3048	0.1229	0.1912	13.5587	11.2332	-89.6069
8	1.5417	-0.3859	0.2807	1.0824	-0.7095	1.2993	-0.0563	0.1102	0.1239	0.0877	-0.1617	-0.2081	-0.1074	0.5538	0.1644	0.1217	-0.011	-0.0101	0.2775	0.0887	0.1758	14.9051	5.7549	-76.7418
9	1.5452	0.6524	0.4315	1.9507	0.5962	2.7644	0.083	-0.0659	-0.27	0.1186	-0.1115	-0.1362	0.4842	0.1442	0.0234	0.1755	0.0543	0.0049	0.2049	0.0843	0.175	9.0574	-6.8132	-75.6479
10	1.7007	-0.1865	0.5397	1.5524	-0.2909	2.867	0.062	-0.1489	-0.3897	-0.0229	0.0202	0.0698	0.7558	-0.4429	-0.0391	0.2505	-0.076	0.0063	0.2556	0.0253	0.2188	-6.3427	-9.8715	-87.5669
11	0.9472	-0.0039	0.5493	0.3541	-0.3263	2.6087	0.0554	0.0946	-0.2023	-0.114	-0.0388	-0.0171	0.4514	-0.0984	-0.0211	0.184	0.002	0.0151	0.181	0.0189	0.1718	-1.3484	-5.5489	-89.8886
12	1.4338	0.2432	-0.4675	0.713	-1.3538	4.9475	-0.0217	0.0358	-0.01	-0.0396	0.0344	0.0478	-0.1457	-0.5334	0.0155	0.0927	0.01	-0.0024	0.2736	0.0037	0.173	-8.589	2.6509	-94.7167

Refinement TLS group

ID	Refine-ID	Refine TLS-ID	Selection details
1	X-RAY DIFFRACTION	1	chain 'A' and (resid 162 through 285 )
2	X-RAY DIFFRACTION	2	chain 'A' and (resid 286 through 318 )
3	X-RAY DIFFRACTION	3	chain 'A' and (resid 319 through 382 )
4	X-RAY DIFFRACTION	4	chain 'A' and (resid 383 through 436 )
5	X-RAY DIFFRACTION	5	chain 'A' and (resid 437 through 548 )
6	X-RAY DIFFRACTION	6	chain 'A' and (resid 549 through 607 )
7	X-RAY DIFFRACTION	7	chain 'B' and (resid 162 through 285 )
8	X-RAY DIFFRACTION	8	chain 'B' and (resid 286 through 344 )
9	X-RAY DIFFRACTION	9	chain 'B' and (resid 345 through 382 )
10	X-RAY DIFFRACTION	10	chain 'B' and (resid 383 through 452 )
11	X-RAY DIFFRACTION	11	chain 'B' and (resid 453 through 548 )
12	X-RAY DIFFRACTION	12	chain 'B' and (resid 549 through 608 )

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

Version 3 of the EMDB header file is now the official format.
The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

+
Jul 12, 2017. Major update of PDB

-
Yorodumi

Thousand views of thousand structures

Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

-
Movie

-
Structure viewers

+
Viewer log

-
This page

-
This web site

-
Options

+
Open data

-
Basic information

-
Structure visualization

-
Downloads & links

-
Download

-
Validation report

-
Related structure data

-
Links

-
Assembly

-
Components

-
Protein , 1 types, 2 molecules AB

-
Non-polymers , 5 types, 690 molecules

-
Details

-
Experimental details

-
Experiment

-
Sample preparation

-
Data collection

-
Processing

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

-
Aug 12, 2020. Covid-19 info

+
Mar 5, 2020. Novel coronavirus structure data

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

+
Jul 12, 2017. Major update of PDB

-
Yorodumi

-Movie

-Structure viewers

+Viewer log

-This page

-This web site

-Options

+Open data

-Basic information

-Structure visualization

-Downloads & links

-Download

-Validation report

-Related structure data

-Links

-Assembly

-Components

-Protein , 1 types, 2 molecules AB

-Non-polymers , 5 types, 690 molecules

-Details

-Experimental details

-Experiment

-Sample preparation

-Data collection

-Processing

+About Yorodumi

-News

-Feb 9, 2022. New format data for meta-information of EMDB entries

-Aug 12, 2020. Covid-19 info

+Mar 5, 2020. Novel coronavirus structure data

+Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

+Jul 12, 2017. Major update of PDB

-Yorodumi

-
Movie

-
Structure viewers

+
Viewer log

-
This page

-
This web site

-
Options

+
Open data

-
Basic information

-
Structure visualization

-
Downloads & links

-
Download

-
Validation report

-
Related structure data

-
Links

-
Assembly

-
Components

-
Protein , 1 types, 2 molecules AB

-
Non-polymers , 5 types, 690 molecules

-
Details

-
Experimental details

-
Experiment

-
Sample preparation

-
Data collection

-
Processing

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

-
Aug 12, 2020. Covid-19 info

+
Mar 5, 2020. Novel coronavirus structure data

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

+
Jul 12, 2017. Major update of PDB

-
Yorodumi